How better planning and behaviour regulation may lead to eating less fat

New research suggests coaching overweight or obese pregnant women to improve their ability to plan and progress toward goals may be vital to helping them lower the amount of fat in their diet.

Maternal diet quality affects prenatal development and long-term child health outcomes. Still, the stress that typically increases during pregnancy – often heightened by concern for fetal health and anxiety over impending parenthood – may derail efforts to focus on healthful eating, previous research has shown.  

In this new study, researchers at The Ohio State University set out to identify the pathway between stress and total fat consumption, with a broader goal to evaluate an intervention designed to improve the diets of pregnant women who are overweight or obese.

Through a series of questionnaires and statistical analysis, the team found that two thinking-related skills – planning and execution of those plans – were weakened in women whose stress was high, and those skill gaps were associated with higher total fat intake.

These two skills are executive functions, a set of multiple thinking processes that enable people to plan, monitor behavior and execute their goals.

“People with a higher stress level tend to have a higher fat intake, too. If stress is high, we’re so stressed out that we’re not thinking about anything – and we don’t care what we eat,” said lead author Mei-Wei Chang, associate professor of nursing at Ohio State.

“That’s why we focused on executive functions as a mediator between stress and diet. And with this baseline data, we have reasons to believe that designing an intervention around executive functions could improve dietary outcomes,” she said. “I would anticipate the results could be similar for nonpregnant women because it’s all about how people behave.”

The study was published recently in the Journal of Pediatrics, Perinatology and Child Health.

The 70 women enrolled in the study had a pre-pregnancy body mass index of between 25 (scores between 25 and 29.9 are categorized as overweight) and 45 (scores of 30 and higher are categorized as obese).

The participants completed questionnaires assessing both overall perceived stress and pregnancy-related stress, as well as executive functions – specifically focusing on metacognition, the ability to plan, and behaviour regulation, the ability to execute those plans. They also completed two 24-hour dietary recalls of their calorie intake and consumption of total fat, added sugar, and fruits and vegetables.

“We were interested in the mediation role of executive functions. The mediator is what makes everything happen,” Chang said. “We wanted to know: If we focus intervention on executive functions, would that carry through to behaviour change in dietary intake?

“Weight loss interventions often involve a prescribed diet or meal plan, and you are told to follow it. But that doesn’t lead to behaviour change in the long term.”

Statistical modelling showed that higher perceived stress was associated with a worsened ability to plan and monitor behaviour, and that pathway was linked to higher total fat intake. Similarly, higher levels of pregnancy-related stress were associated with a lower ability to plan, which in turn was associated with the worsened ability to monitor behaviours related to carrying out the plan – and these factors were linked to higher fat consumption.

These pathways suggested that an intervention designed to lower stress would function as a starting point to improve the diet and enhancing skills through coaching – emphasizing the ability to plan, including being flexible with planning, and behaviour monitoring, particularly when making food choices – would be key to changing eating patterns.

“You need to improve executive functions, and you also need to lower stress,” Chang said. She and colleagues are now analyzing data on the effectiveness of an intervention for the study participants that emphasized stress management and boosting executive function to promote healthy eating.

A specific region of the brain regulates executive functions, and strengths or weaknesses in these skill areas are thought to be affected by various physiological factors. Previous research has found that executive function deficits are more likely to occur in women who are overweight or obese than in women whose weight is average.

“Executive function is not well-studied, and it is not related to intelligence. But people with low executive function cannot make detailed plans and stick to them, and that’s how they get into trouble,” Chang said. “Metacognition and behaviour regulation must go hand in hand – that way you have a much better chance to control your behaviours, and then you will eat better.”

Type 1 diabetes: Maintaining the enzyme ACE2 in the gut prevents diabetic blindness

Maria Grant


Maria Grant

 The leading cause of blindness in American adults is diabetic retinopathy, progressive damage to blood vessels in the light-sensitive tissue at the back of the eye. Yet the source of this damage appears to lie in the belly — mainly a leaky small intestine that weakens the barrier between gut bacteria and the blood system, according to a study published in the journal Circulation Research.

The research blood from human subjects with Type 1 diabetes and a mouse model of Type 1 diabetes were used to explore mechanisms underlying diabetic retinopathy. The results show a way to possibly prevent, or even reverse, eye damage.

“To our knowledge, this study represents the first time that gut barrier disruption has been implicated in the pathogenesis of diabetic retinopathy and also directly links gut leakage with retinopathy severity in human subjects with Type 1 diabetes,” said Maria Grant, M.D., leader of the research team and a professor in the University of Alabama at Birmingham Department of Ophthalmology and Visual Sciences.

Some background is useful to understand Grant’s research.

First, it is known that Type 1 diabetes dysregulates the systemic renin-angiotensin system, or RAS. RAS is a system of hormones and enzymes that regulates blood pressure and other metabolic changes. Besides systemic RAS, there are also local RAS networks that act in diverse tissues. One key RAS enzyme is ACE2, or angiotensin-converting enzyme 2. The loss of ACE2 in diabetes activates the vasodeleterious RAS axis and lessens the vasoprotective RAS axis. Intriguingly, in a mouse model of Type 1 diabetes, feeding mice with a modified gut bacterial strain of Lactobacillus paracasei, which was engineered to produce human ACE2, protects the mice against diabetic retinopathy progression. Finally, lack of ACE2 in the gut was known to increase gut permeability and systemic inflammation.

The human studies, published in Prasad, Floyd et al., Circulation Research, compared people with Type 1 diabetes versus controls. The subjects with Type 1 diabetes were further stratified into three groups: no diabetic retinopathy, non-proliferative diabetic retinopathy and the more serious disease called proliferative diabetic retinopathy. By measuring levels of certain immune cells and biomarkers in the blood, including gut microbial antigens, the researchers found that human subjects with retinopathy had a dysregulated systemic RAS and profound gut permeability defects that activated components of both the adaptive and innate immune response. Furthermore, increases in the severity of diabetic retinopathy were found to correlate with increased levels of gut permeability biomarkers and a gut microbial antigen. This included increased levels of angiotensin II, the RAS hormone that activates the vasodeleterious RAS axis.

Using the Akita mouse-Type 1 diabetes model, researchers first gave the ACE2-producing Lactobacillus paracasei, developed by Qiuhong Li, Ph.D., from the University of Florida, to the mice orally beginning at the onset of diabetes. This probiotic treatment prevented the loss of gut epithelial ACE2 typically seen in Akita mice, and importantly, it prevented intestinal epithelial and endothelial barrier damage. It also reduced the high blood sugar levels known as hyperglycemia.

When the oral ACE2-producing Lactobacillus paracasei treatment was withheld until six months after diabetes was established, that delayed treatment reversed the gut barrier dysfunction and diabetic retinopathy that had already formed in the mice, including reducing the number of damaged capillaries in the retina.

Grant and colleagues also found evidence for several mechanisms that contributed to the ACE2-reduced gut barrier damage and ACE2-lowering of blood sugar. To validate results from the Akita/ACE2-producing Lactobacillus paracasei model, they created a second model — a genetically modified Akita strain that overexpresses human ACE2 in small intestine epithelial cells.

“The significance of the work is we demonstrated that dysregulated intestinal RAS results in translocation of gut microbial antigens into the plasma,” Grant said. “These bacterial peptides activate the endothelium via toll-like receptors, creating an inflammatory endothelium that has been strongly implicated in the pathogenesis of vascular diseases, including diabetic retinopathy.

“We demonstrated loss of intestinal barrier function in human subjects with Type 1 diabetes using gut barrier biomarkers, and this increase in permeability was associated with gut-derived immune cell activation.”

Study identifies potential new approach for treating lupus

Researchers identify new approach for treating lupus


Jeffrey Rathmell, PhD, (left), and Kelsey Voss, PhD, led a multidisciplinary team that identified iron metabolism in T cells as a potential target for treating lupus. CREDIT Vanderbilt University Medical Center

Targeting iron metabolism in immune system cells may offer a new approach for treating systemic lupus erythematosus (SLE) — the most common form of the chronic autoimmune lupus.

A multidisciplinary team of investigators at Vanderbilt University Medical Center has discovered that blocking an iron uptake receptor reduces disease pathology and promotes the activity of anti-inflammatory regulatory T cells in a mouse model of SLE. The findings were published Jan. 13 in the journal Science Immunology

Lupus, including SLE, occurs when the immune system attacks a person’s own healthy tissues, causing pain, inflammation and tissue damage. Lupus most commonly affects skin, joints, brain, lungs, kidneys and blood vessels. About 1.5 million Americans and 5 million people worldwide have a form of lupus, according to the Lupus Foundation of America. 

Treatments for lupus aim to control symptoms, reduce immune system attack of tissues, and protect organs from damage. Only one targeted biologic agent has been approved for treating SLE, belimumab in 2011. 

“It has been a real challenge to come up with new therapies for lupus,” said Jeffrey Rathmell, PhD, professor of Pathology, Microbiology and Immunology and Cornelius Vanderbilt Chair in Immunobiology. “The patient population and the disease are heterogeneous, which makes it difficult to design and conduct clinical trials.” 

Rathmell’s group has had a long-standing interest in lupus as part of a broader effort to understand mechanisms of autoimmunity. 

When postdoctoral fellow Kelsey Voss, PhD, began studying T cell metabolism in lupus, she noticed that iron appeared to be a “common denominator in many of the problems in T cells,” she said. She was also intrigued by the finding that T cells from patients with lupus have high iron levels, even though patients are often anemic. 

“It was not clear why the T cells were high in iron, or what that meant,” said Voss, first author of the Science Immunology paper. 

To explore T cell iron metabolism in lupus, Voss and Rathmell drew on the expertise of other investigators at VUMC: 

  • Eric Skaar, PhD, and his team are experienced in the study of iron and other metals; 
  • Amy Major, PhD, and her group provided a mouse model of SLE; and 
  • Michelle Ormseth, MD, MSCI, and her team recruited patients with SLE to provide blood samples. 

First, Voss used a CRISPR genome editing screen to evaluate iron-handling genes in T cells. She identified the transferrin receptor, which imports iron into cells, as critical for inflammatory T cells and inhibitory for anti-inflammatory regulatory T cells. 

The researchers found that the transferrin receptor was more highly expressed on T cells from SLE-prone mice and T cells from patients with SLE, which caused the cells to accumulate too much iron. 

“We see a lot of complications coming from that — the mitochondria don’t function properly, and other signaling pathways are altered,” Voss said. 

An antibody that blocks the transferrin receptor reduced intracellular iron levels, inhibited inflammatory T cell activity, and enhanced regulatory T cell activity. Treatment of SLE-prone mice with the antibody reduced kidney and liver pathology and increased production of the anti-inflammatory factor, IL-10. 

“It was really surprising and exciting to find different effects of the transferrin receptor in different types of T cells,” Voss said. “If you’re trying to target an autoimmune disease by affecting T cell function, you want to inhibit inflammatory T cells but not harm regulatory T cells. That’s exactly what targeting the transferrin receptor did.” 

In T cells from patients with lupus, expression of the transferrin receptor correlated with disease severity, and blocking the receptor in vitro enhanced production of IL-10. 

The researchers are interested in developing transferrin receptor antibodies that bind specifically to T cells, to avoid any potential off-target effects (the transferrin receptor mediates iron uptake in many cell types). They are also interested in studying the details of their unexpected discovery that blocking the transferrin receptor enhances regulatory T cell activity. 

Skaar is the Ernest W. Goodpasture Professor of Pathology and director of the Vanderbilt Institute for Infection, Immunology, and Inflammation. Major, associate professor of Medicine, and Ormseth, assistant professor of Medicine, are faculty members in the Division of Rheumatology and Immunology. Rathmell is the director of the Vanderbilt Center for Immunobiology. 

Rx for prolonged sitting: A five-minute stroll every half hour


Mounting evidence suggests prolonged sitting—a staple of modern-day life—is hazardous to your health, even if you exercise regularly. Based on these findings, doctors advise all adults to sit less and move more.

But how often do we need to get up from our chairs? And for how long? 

Few studies have compared multiple options to determine the answer most office workers want: What is the least amount of activity needed to counteract the health impact of a workday filled with sitting?

A study by Columbia University exercise physiologists has an answer: just five minutes of walking every half hour during prolonged sitting can offset some of the most harmful effects.

The study, led by Keith Diaz, PhD, associate professor of behavioural medicine at Columbia University Vagelos College of Physicians and Surgeons, was published online in Medicine & Science in Sports & Exercise, the journal of the American College of Sports Medicine.

Unlike other studies that test one or two activity options, Diaz’s study tested five different exercise “snacks”: one minute of walking after every 30 minutes of sitting, one minute after 60 minutes; five minutes every 30; five minutes every 60; and no walking. 

“If we hadn’t compared multiple options and varied the frequency and duration of the exercise, we would have only been able to provide people with our best guesses of the optimal routine,” Diaz says.

Each of the 11 adults who participated in the study came to Diaz’s laboratory. Participants sat in an ergonomic chair for eight hours, rising only for their prescribed exercise snack of treadmill walking or a bathroom break. Researchers kept an eye on each participant to ensure they did not over- or under-exercise and periodically measured their blood pressure and blood sugar (key indicators of cardiovascular health). Participants were allowed to work on a laptop, read, and use their phones during the sessions and were provided standardized meals.

The optimal amount of movement, the researchers found, was five minutes of walking every 30 minutes. This was the only amount that significantly lowered blood sugar and blood pressure. In addition, this walking regimen dramatically affected how the participants responded to large meals, reducing blood sugar spikes by 58% compared with sitting all day.

Taking a walking break every 30 minutes for one minute also provided modest benefits for blood sugar levels throughout the day, while walking every 60 minutes (either for one minute or five minutes) provided no benefit.

All walking significantly reduced blood pressure by 4 to 5 mmHg compared with sitting all day. “This is a sizeable decrease, comparable to the reduction you would expect from exercising daily for six months,” says Diaz.

The researchers also periodically measured participants’ mood, fatigue, and cognitive performance levels during the testing. All walking regimens, except walking one minute every hour, led to significant decreases in fatigue and significant improvements in mood. None of the walking regimens influenced cognition.

“The effects on mood and fatigue are important,” Diaz says. “People tend to repeat behaviours that make them feel good and enjoyable.”

The Columbia researchers are currently testing 25 different doses of walking on health outcomes and testing a wider variety of people: Participants in the current study were in their 40s, 50s, and 60s, and most did not have diabetes or high blood pressure. 

“What we know now is that for optimal health, you need to move regularly at work, in addition to a daily exercise routine,” says Diaz. “While that may sound impractical, our findings show that even small amounts of walking spread through the workday can significantly lower your risk of heart disease and other chronic illnesses.”

Medical clowns: A significant contribution to medical care – Much more than just entertainment

A first study of its kind by Tel Aviv University researchers examined the “secret magic” of medical clowns


According to researchers from Tel Aviv University and the Israel Center for Medical Simulation: “medical clowns not only help the patients, but they also help the parents, the medical team, and the achievement of therapeutic goals. In fact, through various communication skills, clowns enable patients to overcome crises and move towards healing.”

Not just fun and games: a new study tested and categorized the skills of medical clowns found that their importance goes far beyond just creating a good mood for patients. The researchers identified 40 different skills of medical clowns, including establishing an emotional connection and creating a personal relationship with the patient, expressing the patient’s voice about his/her frustrations and difficulties to the medical staff, increasing the patient’s motivation to adhere to the medical treatment, distracting the patient from pain, and creating an atmosphere of games and play. The findings emphasize that the importance of clowns goes far beyond “providing just a good mood” for patients.

The research was conducted under the leadership of Prof. Orit Karnieli-Miller, with Dr. Lior Rosenthal, both from the Department of Medical Education at Tel Aviv University, in collaboration with Ms. Orna Divon-Ophir, Dr. Doron Sagi, Prof. Amitai Ziv and Ms. Liat Pessach-Gelblum from the Israel Center for Medical Simulation (MSR). The study was published in Qualitative Health Research, a leading journal in the field of health.

Prof. Orit Karnieli-Miller

Prof. Orit Karnieli-Miller CREDITTel Aviv University

The researchers show that medical clowns not only help the patients and their family members, but also the medical team and the achievement of treatment goals. Through use of different communication skills, clowns make it easier for the patient to cooperate with one or another treatment. The medical clowns work in a team with other therapists and know how to intervene and help when an argument or crisis arises, and help overcome it and advance treatment.

Earlier studies showed medical clowns as trained professionals whose goal is to change the hospital environment through humor. Studies conducted throughout the years have shown the clowns’ positive influence on this and in helping patients deal with pain. However, so far, no studies have empirically mapped the skills they use and their therapeutic goals to help understand their “secret magic.” In addition, there was a lack of broad understanding of how clowns can help children, teenagers, and their parents in various challenging situations of distress and difficulty, as well as how they can help patients and medical teams achieve treatment goals. This lack of appreciation of the potential benefits of utilizing the services of a medical clown meant that sometimes patients and medical teams could be reluctant to cooperate with them.

As part of the new study, the team of researchers focused on qualitative, in-depth systematic identification of the skills of medical clowns through observation and analysis of their actions in challenging encounters with adolescents, parents, and medical staff. The team analyzed videotaped sessions of medical clowns in various simulated situations and conducted in-depth interviews with expert medical clowns. The researchers identified forty different skills used by the medical clowns to achieve four therapeutic goals: 1) building a relationship and connecting to the needs and desires of the patients; 2) dealing with emotions and difficulties; 3) increasing the patient’s motivation to adhere to the treatment plan; and 4) increasing the patient’s sense of control and providing encouragement to patients.

The clowns examined in the study were trained and recruited by the “Dream Doctors Project”, a non-profit association that employs medical clowns as part of the paramedical system in Israeli hospitals, and trains them to work within multi-disciplinary teams. The Tel Aviv University researchers collaborated with the Israel Center for Medical Simulation (MSR), which created a simulation-based workshop focused on developing the skills of experienced medical clowns.

Prof. Karnieli-Miller: “from the moment they enter the room, the clowns form a bond with the patients, strengthen them, and give them power and status within the medical system. They do this through an initial connection to the patients’ voice, and even to the patients’ reluctance to implement therapeutic recommendations – an emotional connection that often results in the patient changing their position and cooperating with the medical staff. The medical system is hierarchical, and it is not always easy for patients to navigate. Therefore, one of the skills of medical clowns is to place themselves in the lowest position in the medical setting. By doing so they empower the patients, giving the patients power and control, including the choice of whether to allow the clown to enter the room as well as to dictate the nature of the patient’s role vis-à-vis that of the clown. This provides an increased sense of control and gives the patient courage to face their challenges.”

The researchers emphasize that the clowns are very aware of the emotional difficulty associated with staying in a hospital and dealing with an illness. To deal with these issues the clowns sometimes distract the patient by using props, humor, and imagination. Other skills include the clowns allowing the patient to direct their frustrations towards them, away from the medical staff or parents. Depending on the situation the clowns may also use a comforting touch, soothing music, empathetic listening, or a reinforcing statement to provide an environment where the patient feels comfortable to express their feelings. A patient’s ability to gain legitimacy is important and is strengthened by the clowns. Prof. Karnieli-Miller adds: “Mapping the skills and goals of the medical clowns improves their understanding of their role and may help other health professionals appreciate their work methods and the benefits of incorporating these methods into their own practices when faced with similar challenges.”

Prof. Karnieli-Miller concludes: “This research is important because it allows the clowns to enhance their training program and refine their diverse skills to achieve the various therapeutic goals appropriate for different patients, as well as helping health professionals collaborate with the medical clowns. If professionals in the healthcare field will know how and when to cooperate with the medical clowns, they will be able to help patients overcome challenges, and at the same time they may be more tolerant of the clowns’ ‘disruption’ of the hospital care regimen. This appreciation of the clowns’ contribution will provide the clowns with the time and space to connect with patients and help and encourage patients to become more active participants in their treatment plan. Important goals all health professionals aspire to.”